Holographic display system for restoration of sight to the blind.

OBJECTIVE: We present a holographic near-the-eye display system enabling optical approaches for sight restoration to the blind, such as photovoltaic retinal prosthesis, optogenetic and other photoactivation techniques. We compare it with conventional liquid crystal displays (LCD) or digital light processing (DLP)-based displays in terms of image quality, field of view, optical efficiency and safety. APPROACH: We detail the optical configuration of the holographic display system and its characterization using a phase-only spatial light modulator. MAIN RESULTS: We describe approaches to controlling the zero diffraction order and speckle related issues in holographic display systems and assess the image quality of such systems. We show that holographic techniques offer significant advantages in terms of peak irradiance and power efficiency, and enable designs that are inherently safer than LCD or DLP-based systems. We demonstrate the performance of our holographic display system in the assessment of cortical response to alternating gratings projected onto the retinas of rats. SIGNIFICANCE: We address the issues associated with the design of high brightness, near-the-eye display systems and propose solutions to the efficiency and safety challenges with an optical design which could be miniaturized and mounted onto goggles.

Photovoltaic retinal prosthesis: implant fabrication and performance.

The objective of this work is to develop and test a photovoltaic retinal prosthesis for restoring sight to patients blinded by degenerative retinal diseases. A silicon photodiode array for subretinal stimulation has been fabricated by a silicon-integrated-circuit/MEMS process. Each pixel in the two-dimensional array contains three series-connected photodiodes, which photovoltaically convert pulsed near-infrared light into bi-phasic current to stimulate nearby retinal neurons without wired power connections. The device thickness is chosen to be 30 µm to absorb a significant portion of light while still being thin enough for subretinal implantation. Active and return electrodes confine current near each pixel and are sputter coated with iridium oxide to enhance charge injection levels and provide a stable neural interface. Pixels are separated by 5 µm wide trenches to electrically isolate them and to allow nutrient diffusion through the device. Three sizes of pixels (280, 140 and 70 µm) with active electrodes of 80, 40 and 20 µm diameter were fabricated. The turn-on voltages of the one-diode, two-series-connected diode and three-series-connected diode structures are approximately 0.6, 1.2 and 1.8 V, respectively. The measured photo-responsivity per diode at 880 nm wavelength is ∼0.36 A W(-1), at zero voltage bias and scales with the exposed silicon area. For all three pixel sizes, the reverse-bias dark current is sufficiently low (<100 pA) for our application. Pixels of all three sizes reliably elicit retinal responses at safe near-infrared light irradiances, with good acceptance of the photodiode array in the subretinal space. The fabricated device delivers efficient retinal stimulation at safe near-infrared light irradiances without any wired power connections, which greatly simplifies the implantation procedure. Presence of the return electrodes in each pixel helps to localize the current, and thereby improves resolution.

Hepatitis A antibody prevalence among young adults in Israel--the decline continues.

This study sought to determine whether the decline in prevalence of hepatitis A virus (HAV) antibodies detected in Israel in 1977, 1984, and 1987 has continued. The anti-HAV antibody prevalence of a systematic sample of 578 male and female recruits inducted into the Israel Defence Force in 1996 was 38.4%. The reduction in antibody prevalence from 1977 (64%) was highly significant (P < 0.001). There was a smaller decrease rate in recruits of European, North American, Australian and South African origin than from elsewhere. A 'strategy' that uses active immunization against hepatitis A (inactivated vaccine, instead of gamma globulin) should be considered, particularly in high risk groups such as field units during military service.

Meningococcal polysaccharide vaccination of military recruits in Israel: preliminary assessment of vaccine effect.

Meningococcal disease in the Israel Defense Force is caused mainly by serogroups C and Y. Immunization of recruits with quadrivalent polysaccharide vaccine was introduced in November 1994. The person-time incidence rate dropped from 1.33 cases per 100,000 person-years for the preceding decade to 0 for the 32 months following immunization (p = 0.025).

Influenza vaccine efficacy in young, healthy adults.

Findings concerning influenza vaccine efficacy in young, healthy adults are inconsistent. A high incidence of influenza in the winter of 1995 provided an opportunity to study the efficacy of influenza vaccine among young, healthy military personnel. Influenza activity was confirmed by isolation of influenza A and B viruses from nasopharyngeal swab specimens from hospitalized soldiers. Self-administered questionnaires concerning vaccination status and disease symptoms were used in two study groups: recruits and veteran soldiers serving in different camps. Six hundred eighty-four individuals had received influenza vaccine and 652 had not. Vaccine efficacy was found to be 38.1% (P = .002) for preventing febrile illness with or without symptoms and slightly higher (41.6%; P < .001) for preventing fever together with upper respiratory tract symptoms. The current influenza vaccine significantly reduced febrile illness among healthy military personnel.

Major adverse reactions to yeast-derived hepatitis B vaccines--a review.

Yeast-derived recombinant DNA hepatitis B vaccines usage became widely accepted since the early 1990s. Severe adverse events have been reported infrequently in adults and rarely in infants and children given hepatitis B vaccine in the ten years which have passed since the introduction of the vaccine. Some of the data were summarized in previous review articles. Our review of the literature revealed reports of serious adverse reactions which included immediate reactions (anaphylaxis and urticaria) as well as delayed reactions, including skin, rheumatic, vasculitic (including Systemic Lupus Erythematosus and glumerulonephritis), hematologic, ophthalmologic and neurologic reactions. These cases were summarized and a pathogenetic mechanism is offered.

Is the coexistence of mutations in the genes of factor V and MTHFR a predisposing factor for massive skin necrosis due to loxoscelism?

A 28-year-old previously healthy man was diagnosed as having an extensive necrotic lesion of his calf due to loxoscelism. One year later he was diagnosed as having co-inheritance of mutations in factor V and methyl tetrahydrofolate reductase (MTHFR). This is the first report of a possible etiologic connection between loxoscelism necrotic lesions and thrombogenic diseases.

[Epidemiological characteristics of outbreaks of diarrhea and food poisoning in the Israel Defense Forces in the years 1978-1995].

Acute infectious diseases of the gastrointestinal tract and food poisoning are problems of great importance in the Israel Defense Forces (IDF). They involve individual and epidemic morbidity, with impairment of health of individual soldiers and in the activities of units. Outbreaks of gastrointestinal infectious diseases must be reported to the IDF army health branch, which conducts epidemiological investigation. This study is based on data from yearly epidemiological reports for 1978-1989, and from a computerized database for the years 1990-1995. The incidence of outbreaks is characterized by an unstable trend. It was highest at the end of the 80's (68.3 per 100,000 soldiers on active duty) and lowest for the last 2 years (1994-1995, 36.3 per 100,000). The incidence of soldiers involved in food-borne outbreaks has been more stable, constantly declining during the course of the years. There was marked seasonality with a peak in the summer months. Sporadic morbidity was constant in 1990-1995, with a yearly attack rate of 60% in soldiers on active duty. Shigella strains were the leading cause of outbreaks until 1993, while in 1994-1995 their proportion decreased, with an increase in the proportion of Salmonella strains. As to Staphylococcus aureus, its role in causing food poisoning has been characterized by marked changes. Shigella sonnei replaced Shigella flexneri as the leading strain. 73.3% of outbreaks were small, with fewer than 40 soldiers involved, while 5.4% of outbreaks affected more than 100 soldiers. Outbreaks in which a bacterial agent was identified or which occurred in new-recruit bases were larger than those in which a bacterial agent was not identified, or which occurred in active field unit bases. In conclusion, the rates of infectious disease of the gastrointestinal tract are still high, although there has been a marked decrease since 1994. The incidence of outbreaks has also decreased, as well as the role of Shigella as a leading causative agent.

Identification of common motifs in unaligned DNA sequences: application to Escherichia coli Lrp regulon.

We describe a relatively simple method for the identification of common motifs in DNA sequences that are known to share a common function. The input sequences are unaligned and there is no information regarding the position or orientation of the motif. Often such data exists for protein-binding regions, where genetic or molecular information that defines the binding region is available, but the specific recognition site within it is unknown. The method is based on the principle of 'divide and conquer'; we first search for dominant submotifs and then build full-length motifs around them. This method has several useful features: (i) it screens all submotifs so that the results are independent of the sequence order in the data; (ii) it allows the submotifs to contain spacers; (iii) it identifies an existing motif even if the data contains 'noise'; (iv) its running time depends linearly on the total length of the input. The method is demonstrated on two groups of protein-binding sequences: a well-studied group of known CRP-binding sequences, and a relatively newly identified group of genes known to be regulated by Lrp. The Lrp motif that we identify, based on 23 gene sequences, is similar to a previously identified motif based on a smaller data set, and to a consensus sequence of experimentally defined binding sites. Individual Lrp sites are evaluated and compared in regard to their regulation mode.

Repeat infusion of recombinant tissue-type plasminogen activator in patients with acute myocardial infarction and early recurrent myocardial ischemia.

When conventional treatment of patients with early clinical reinfarction after thrombolytic therapy fails, mechanical revascularization may be attempted. An alternative strategy, repeat thrombolytic infusions, is reported. Fifty-two patients with acute myocardial infarction were treated with one or two additional thrombolytic infusions of recombinant tissue-type plasminogen activator (rt-PA) because of nonsustained ischemia after initial treatment with rt-PA or streptokinase. Thirty-five patients received the second infusion within 1 h of the first; 13 patients received the second infusion 1 to 72 h after the first and 4 patients received it later during their hospitalization. Bleeding complications occurred in 10 patients (19%); however, most of these were minor (no intracranial bleeding) and only 2 patients required blood transfusion. In 14 patients in whom the decrease in fibrinogen and plasminogen levels was measured after the first and second infusions, this decrease was only 25% and 63%, respectively--only slightly higher than the 22% and 53% decreases measured in 63 patients who had only one rt-PA infusion. In 44 patients (85%), the acute ischemia resolved completely within 1 h after initiation of the second infusion. In 23 patients (44%), pain and ST segment elevation did not recur and invasive coronary intervention was avoided. Thus, repeat rt-PA infusions can stabilize a substantial number of patients with acute reinfarction and, even when relief is temporary, repeat rt-PA infusions can minimize myocardial damage while patients await mechanical revascularization.